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Hydrophobic Nanoparticles Reduce the β-sheet content of SEVI Amyloid Fibrils and Inhibit SEVI-Enhanced HIV Infectivity.

Hydrophobic Nanoparticles Reduce the β-sheet content of SEVI Amyloid Fibrils and Inhibit SEVI-Enhanced HIV Infectivity.
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Sheik DA, Chamberlain JM, Brooks LR, Clark ML, Kim YH, Leriche G, Kubiak CP, Dewhurst S, Yang J,


Sheik DA, Chamberlain JM, Brooks LR, Clark ML, Kim YH, Leriche G, Kubiak CP, Dewhurst S, Yang J, (click to view)

Sheik DA, Chamberlain JM, Brooks LR, Clark ML, Kim YH, Leriche G, Kubiak CP, Dewhurst S, Yang J,

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Langmuir : the ACS journal of surfaces and colloids 2017 02 16() doi 10.1021/acs.langmuir.6b04295

Abstract

Semen-Derived Enhancer of Virus Infection (SEVI) fibrils are naturally abundant amyloid aggregates found in semen that facilitate viral attachment and internalization of HIV in cells, thereby increasing the probability of infection. Mature SEVI fibrils are comprised of aggregated peptides exhibiting high β-sheet secondary structural characteristics. Herein, we show that polymers containing hydrophobic side chains can interact with SEVI and reduce its β-sheet content by ~45% compared to the β-sheet content of SEVI in the presence of polymers with hydrophilic side chains, as estimated by Polarization Modulation-Infrared Reflectance Absorption Spectroscopy Measurements. A nanoparticle formulation of this hydrophobic polymer reduced SEVI-mediated HIV infection in TMZ-bl cells by 60% compared to control treatment. While these nanoparticles lacked specific amyloid-targeting groups, thus, requiring high concentrations to observe biological activity, the use of hydrophobic interactions to alter the secondary structure of amyloids represents a useful approach to neutralizing SEVI function. These results could, therefore, have general implications in the design of novel materials that can modify the activity of amyloids associated with a variety of other neurologic and systemic diseases.

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